6rsg
From Proteopedia
NMR structure of pleurocidin VA in SDS micelles
Structural highlights
Publication Abstract from PubMedAntimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membranes and seek intracellular targets while also causing membrane damage. Here we describe modification strategies that generate pleurocidin analogues with substantially improved, broad spectrum, antibacterial properties, which are effective in murine models of bacterial lung infection. Increasing peptide-lipid intermolecular hydrogen bonding capabilities enhances conformational flexibility, associated with membrane translocation, but also membrane damage and potency, most notably against Gram-positive bacteria. This negates their ability to metabolically adapt to the AMP threat. An analogue comprising D-amino acids was well tolerated at an intravenous dose of 15 mg/kg and similarly effective as vancomycin in reducing EMRSA-15 lung CFU. This highlights the therapeutic potential of systemically delivered, bactericidal AMPs. A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy.,Manzo G, Hind CK, Ferguson PM, Amison RT, Hodgson-Casson AC, Ciazynska KA, Weller BJ, Clarke M, Lam C, Man RCH, Shaughnessy BGO, Clifford M, Bui TT, Drake AF, Atkinson RA, Lam JKW, Pitchford SC, Page CP, Phoenix DA, Lorenz CD, Sutton JM, Mason AJ Commun Biol. 2020 Nov 27;3(1):697. doi: 10.1038/s42003-020-01420-3. PMID:33247193[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|